Protective role and immunoregulatory effect of CXCR3 in hepatic ischemia- reperfusion injury
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摘要:
目的研究趋化因子受体CXCR3在肝脏缺血再灌注损伤中的作用及机制。方法建立小鼠肝脏缺血再灌注损伤模型,共计48只小鼠,分为手术处理组及假手术组,分别按照手术后3、6、12、24 h取样(每组6只),利用实时荧光定量PCR、Western Blot以及流式细胞仪检测趋化因子CXCL9-11及其受体CXCR3的表达,利用CXCR3的特异性阻断剂C6阻断CXCR3的作用,通过组织形态,肝酶活性评价肝损伤程度,通过流式细胞仪检测浸润炎症细胞的亚群分布等,阐述CXCR3的作用机制。所有数据均以均数±标准差(x±s)为表示,各组之间比较应用单因素方差分析。结果与假手术组相比较,趋化因子CXCL9-11及其受体CXCR3在缺血再灌注后各时间点表达显著增高(P<0.05),阻断CXCR3能够显著保护肝功能及肝脏形态(P<0.05)。CXC3R特异性抑制剂C6能够显著降低Th1细胞的浸润(P<0.01),同时增强Treg细胞的浸润(P<0.01)。结论 CXCR3是一个理想的用于保护肝脏缺血再灌注损伤的治疗靶点,其机制与免疫调节有关。
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关键词:
- 受体,CXCR3 /
- 再灌注损伤 /
- T淋巴细胞亚群 /
- T淋巴细胞,辅助诱导
Abstract:Objective To investigate the role and action mechanism of chemokine (C- X- C motif) receptor 3 (CXCR3) in hepatic ischemia- reperfusion injury (IRI) .Methods Forty- eight mice were divided into operation group and sham- operation group.The operation group was treated to establish a mouse model of IRI.Liver tissues were obtained at 3, 6, 12, and 24 h after IRI, with 6 mice at each time point.The expression of chemokine (C- X- C motif) ligand 9- 11 (CXCL9- 11) and their receptor CXCR3 were measured by real- time PCR and Western blot.The effect of CXCR3 was blocked by its specific antagonist C6.Hepatic injury was estimated based on the activity of hepatic transaminase and morphological indices.The distribution of subsets of infiltrating T cells was analyzed by flow cytometry.All data were expressed as mean ± standard deviation.Comparison between groups was made by one- way analysis of variance.Results Compared with the sham- operation group, the operation group had significantly upregulated expression of CXCL9- 11 and CXCR3 at all time points after IRI (P < 0.05) .Blocking CXCR3 significantly protected liver function and morphology (P < 0.05) .Antagonist C6 significantly reduced Th1 cell infiltration (P < 0.01) , but significantly increased Treg infiltration (P < 0.01) .Conclusion CXCR3 is an ideal therapeutic target in IRI treatment due to its relationship with immunoregulation.
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